Diagnostic accuracy of different cut-off values of adenosine deaminase levels in tuberculous pleural effusion

Objective: To assess the diagnostic accuracy of different cut-off values of pleural fluid adenosine deaminase levels as a diagnostic method for tuberculous pleural effusion. Method: The prospective study was conducted from 2014 to 2016 at the Aga Khan University Hospital, Karachi, and comprised pleural fluid samples of adult patients with and without tuberculosis which were tested for adenosine deaminase levels, and divided into tuberculosis group A and non-tuberculosis group B. Sensitivity, specificity, negative predictive value and positive predictive value were calculated using different cut-offs. Data was analysed using IBM SPSS (Statistical Package for Social Sciences) version 21.0 (IBM Corp., Armonk, NY). Results: Of 155 patients, 46(29.7%) had tuberculosis; 30(65.2%) males and 16(34.8%) females. Those who did not have tuberculosis were 109(70.3%); 69(63.3%) males and 40(36.7%) females. The adenosine deaminase levels were elevated in group A compared to group B (p\u3c0.001). The cut-off of 30U/L showed the highest sensitivity (71.7%) and negative predictive value (87.4%), and a specificity of 82.6%. The cut-off of 50U/L showed the highest specificity (89.9%) with sensitivity 52.2%, and the cut-off of 40U/L showed the highest positive predictive value of 68.9% with sensitivity 67.4% and specificity 87.2%. Conclusion: Pleural fluid adenosine deaminase testing for diagnosing tuberculosis pleuritis revealed highest sensitivity and moderate specificity for cut-off value of 30U/

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

The role of suppressor of cytokine signaling (SOCS1 and SOCS3) molecules in determining severity of tuberculosis infection

Introduction: Mycobacterium tuberculosis the causative agent of tuberculosis (TB), down-regulates host immunity and persists within cells. Cytokines are responsible for immune activation but these are characteristically modulated in TB. Expression of cytokine regulatory molecules Suppressor of Cytokine Signaling (SOCS)-1, SOCS3 and T regulatory cells (FOXP3, Tregs marker) molecules are increased in TB but their association with severity and their role in determining disease outcomes TB is unclear. Objective: We investigated the role of SOCS1, SOCS3 and FOXP3 by studying the expression of cytokines across a spectrum of pulmonary (PTB) and extra-pulmonary (ETB) TB patients in comparison with healthy endemic controls (EC). Materials and Methods: This was a cross-sectional study which was approved by the Ethical Review Committee of the AKU. We recruited ECs (n=30) and patients with P113 (n=33) and ETB (n=33). Healthy volunteers were sub-divided according to their tuberculin skin test (TST) reactivity; EC-TST (-), n=15 or positive EC-TST (+), n=15. Or, according to ESAT-6- induced IFN-y responses; EC-IFN-y (-), n=24 (IFN-y median, 0 pg/mL, IQR 0-0 pg/mL) or EC-IFN-y (+), n=5 (IFN-y median, 64.3 pg/mL, IQR 1.1-79.9 pg/mL). PTB was 1111 classified as moderately advanced (PTB-mod, n=20) and far-advanced (PTB-adv, n=13) 1111 disease. ETB was classified as less (L-ETB, n=26) and more severe (D-ETB, n=7) disease. Gene expression of Thl type cytokines (IFN-y, TNF-a, IL-2, IL-6, IL-17A, 1111 CXCL9, CCL2, and CCR2), Th2 type cytokines (IL-4 and IL-10) and regulatory factors 1111 (SOCS1, SOCS3, T-bet, Gata-3, and FOXP3), secretion of Thl (IFN-y, TNF-a, CXCL9, CXCL10 and CCL2) and Th2 cytokines (IL-10) was determined in peripheral blood cells. 1111 In vitro responses to stimulation with live M tuberculosis (Mtb), sonicated (MTB sonicate, MTBs) and Early secreted antigen target-6 (ESAT-6) was determined in each study subject. Immunohistochemical analysis was performed on biopsy specimens of tuberculous lymphadenitis (LNTB) as compared with un-infected reactive lymph nodes. These were classified histologically according to extent of necrosis present into focal (f-LNTB, n=10) or extensive (e-LNTB, n=8) caseous necrosis. Expression of SOCS1, SOCS3 and CXCR3 was performed in each case. Results: SOCS1 mRNA expression was raised in T cells from PTB (p=0.02) as compared with EC-TST (-). In un-stimulated PBMCs, SOCS1 mRNA levels were increased in PTB-adv as compared with PTB-mod (p=0.008). IL-6 secretion levels were increased in PTB-adv (p=0.012) and L-ETB (p=0.036) while, IL-10 secretion levels were increased in PTB-adv (p=0.012), L-ETB (p=0.003) and D-ETB (p=0.026) as compared with EC-TST (-). Compared to EC-TST (-) subjects, PTB patients in response to live Mtb showed increased SOCS1 mRNA (p=0.0067), while decreased SOCS3 mRNA was observed in both PTB (p=0.028) and ETB (p=0.023). Mtb-induced increased FOXP3 mRNA in ETB as compared with EC-TST (-) (p=0.021) and EC-TST (+) (p=0.038). Compared to EC-TST (-) subjects; Mtb—induced decreased SOCS3 mRNA in PTB-adv (p=0.007), increased FOXP3 mRNA (p=0.017) in L-ETB, increased SOCS1 mRNA in PTB-mod (p=0.022), PTB-adv (1)=0.014) and D-ETB (p=0.009). Further, Mtb-stimulated increased SOCS1 mRNA in PTB-adv (p=0.016) and D-ETB (p=0.027) as compared with L-ETB. ESAT-6—stimulation increased SOCS1 (PTB, p=0.023; ETB, p\u3c0.001) mRNA and decreased IFN-y (PTB, p=0.015; ETB, p=0.009) secretion levels in PTB and ETB as compared with EC-IFN-y (+) subjects. ESAT-6-induced increased IL-10 (p\u3c0.001) secretion levels in PTB as compared with EC-1FN-y (-) subjects. MTBs-induced increased SOCS1 (PTB, p\u3c0.001; ETB, p\u3c0.001) and FOXP3 (PTB, p\u3c0.001; ETB, p\u3c0.001) mRNA in PTB and ETB patients as compared with EC-TST (-) subjects. In granulomas, SOCS1, SOCS3 and CXCR3 protein expression was increased in LNTB as compared with controls. SOCS1 and CXCR3 were mainly associated with extensive as compared with focal caseous necrosis. Conclusions: Increased SOCS 1 mRNA in severe forms of PTB and ETB was associated with increase in IL-6 and IL-10 secretion is reflective of un-favourable disease outcomes. ESAT-6- induced SOCS1 could distinguish latent from active TB. In granulomatous lesions, SOCS1 expression in extensive caseous necrosis was indicative of progressive disseminated infection. Overall, we identify an association of SOCS1 with disease severity in TB. As SOCS1 is a key regulator for determining disease outcomes it may be a possible target for new TB treatment

An audit of contrast extravasation in patients undergoing contrast enhanced CTs at radiology department in a tertiary care hospital in Pakistan

Objective: To audit the radiology department of a health facility, focusing on contrast extravasations management pre- and post-implementation of a standard protocol. Methods: The audit was conducted at the Radiology Department of Shifa International Hospital, Islamabad, Pakistan and comprised reported computed tomography contrast extravasation incidents from January 2017 to December 2019 in the retrospective phase before the implementation of a standard protocol. Post-implementation, re-audit was done prospectively to assess compliance from January 2020 to May 2021. Overall score of >80% was chosen arbitrarily as a qualifying standard for adequate documentation. Results: Of the 49 total cases, 26(53%) related to the first phase and 23(47%) to the second. In the first phase, 2(20%) of the 10 parameters cleared the cut-off mark; 'study performed' 25(96%) and 'limb assessment by technician' 26(100%). In the second phase, 2(20%) parameters failed to clear the cut-off mark; site of cannula/extravasation' 18(78.3%) and 'volume of contrast' 15(65%). Conclusion: Lack of early identification and appropriate management, especially in cases of large-volume extravasation, may result in significant morbidity. Key Words: Contrast extravasation, Contrast-enhanced CT, IV contrast media

Tuberculosis and diabetes mellitus: Relating immune impact of co-morbidity with challenges in disease management in high burden countries

Mycobacterium tuberculosis (MTB) is the causative agent of TB. TB incidence is high in many low resource settings where limited health systems make it difficult for screening of co-morbid conditions. Susceptibility to TB is increased with coincident diabetes mellitus (DM) or prediabetes. DM leads to chronic, subclinical inflammation in the host leading to compromised protective immunity against MTB, impacting TB treatment. This review focuses on the immunological impact of DM and prediabetes on TB infections, highlighting the importance of having effective diagnostic, treatment and management programs for early identification of hyperglycemia in TB patients to improve treatment outcomes. Further, it describes challenges in monitoring of TB and DM co-morbidity in a high-burden setting

Differential Early Secreted Antigen Target (ESAT) 6 kDa–induced IFN-γ and SOCS1 expression distinguishes latent and active tuberculosis

Introduction: Expression of Suppressor of cytokine signaling (SOCS)-1 molecules is increased in patients with tuberculosis (TB). Early Secreted Antigen Target (ESAT)-6 kDa – induced IFN-γ responses indicate Mycobacterium tuberculosis infection. The effect of ESAT6- stimulation on SOCS1 in the host is not known. Methodology: Healthy asymptomatic controls had a negative (n = 16) or a positive ( n = 13) tuberculin skin test (TST). ESAT6-induced IFN- γ responses classified these controls as positive (EC ESAT6 IFN-γ (+), n = 5) or negative (EC ESAT6 IFN-γ (-), n = 24) responders. Patients had pulmonary (n = 21) or extra-pulmonary (n = 30) tuberculosis. Peripheral blood cells were stimulated with ESAT6 and mRNA expression of IFN- γ and SOCS1 was determined. Results: ESAT6-induced IFN-γ expression was raised in EC ESAT6 IFN-γ (+) as compared with EC ESAT6 IFN-γ (-), p = 0.019. ESAT6-induced SOCS1 mRNA expression was increased in both pulmonary TB and extra-pulmonary TB patients as compared with both EC groups. ESAT6-induced IFN-γ/SOCS1 mRNA expression ratio was decreased in TB patients as compared with both EC groups. Conclusion: M. tuberculosis infection induces increased ESAT6-induced IFN- γ responses in both latent and active TB. Our data shows down-regulation of IFN- γ / SOCS1 expression to be induced only in active TB cases, distinguishing them from healthy individuals likely to have latent TB. A decreasing IFN- γ /SOCS1 ratio may leads to reduced Th1 immunity which contributes to inability of the host to control clinical disease